Lecture 14 Antibody-Antigen Reactions
Lecture 14 Antibody-Antigen Reactions
Binding of the epitope in the antigen binding site GOOD FIT POOR FIT antibody combining site antigen determinant high attraction high repulsion low repulsion low attraction
Binding of the epitope in the antigen binding site GOOD FIT POOR FIT antibody combining site antigen determinant high attraction low repulsion high repulsion low attraction
Antibody Avidity Multiple interactions between antigen binding sites and epitopes Greater than additive Similar to VelcroTM More relevant to biologic systems than affinity
Antibody Avidity ◼ Multiple interactions between antigen binding sites and epitopes ◼ Greater than additive ◼ Similar to Velcro™ ◼ More relevant to biologic systems than affinity
Effect of multivalent interactions antibody Fab IgG IgG IgM effective antibody valence 1 2 up to 10 antigen valence 1 1 n n equilibrium constant (L/M) 104 104 107 1011 advantage of multi-valence 103-fold 107-fold definition of bindng affinity affinity avidity avidity intrinsic affinity functional affinity
Effect of multivalent interactions antibody Fab IgG IgG IgM effective antibody valence 1 1 2 up to 10 antigen valence 1 1 n n equilibrium constant (L/M) 104 104 107 1011 advantage of multi-valence - - 103-fold 107-fold definition of bindng affinity affinity avidity avidity intrinsic affinity functional affinity
Biological Consequences of Antibody Affinity/Avidity Neutralization of toxins Complement activation Immune elimination of antigen Virus neutralization More intense immune complex disease in animals higher levels of circulating antigen-antibody complexes more intense localization of immune complexes on basement membranes. more severe impairment of organ function
Biological Consequences of Antibody Affinity/Avidity ◼ Neutralization of toxins ◼ Complement activation ◼ Immune elimination of antigen ◼ Virus neutralization ◼ More intense immune complex disease in animals ◼ higher levels of circulating antigen-antibody complexes ◼ more intense localization of immune complexes on basement membranes. ◼ more severe impairment of organ function